Chemical aspects of compensatory renal hypertrophy.

has been known for over a century that when 1 of the kidneys of a laboratory animal has been surgically removed or is not functioning properly, its partner undergoes a compensatory hypertrophy in which both cell size and cell number increase (20, 21, 33). The mechanism of this compensatory growth is unknown. An obvious possi bility is that it is due to a single kidney having to carry out the work normally shared between 2. In support of this view, it has been claimed that when normal animals are fed diets containing large amounts of sodium chloride (12) or urea (2, 19, 27) or, in particular, protein (3, 26, 28), their kidneys hypertrophy, presumably in response to the addi tional load thrown on them. The renal hypertrophy after such a dietary experiment is, however, much slower than that obtained after unilateral nephrectomy. One difficulty in such investigations has been the lack of a satisfactory method of measuring the extent of kidney growth. The early investigators used kidney weight as a measure of hypertrophy (1, 5). This is obviously un satisfactory since it gives no indication of the chemical changes occurring or of the relative contributions of changes in cell number or in cell size. It is also rather insensitive, since it can be so easily affected by such factors as the blood or urine content of the kidney. More recently, the rate of kidney growth has been assessed by measuring the changes in mitotic frequency (1 1, 36). Although this method is more sensitive than wet kidney weights, it is an index only of the increase in cell number and takes no account of the concomitant increase in cell size. A variation of this method has been the use of isotope incorporation into DNA as an indication of the rate of cell division (30, 31). The present experiments were performed to place the estimation of kidney hypertrophy on a more quantitative basis. For this purpose, the DNA content of the kidney has been used as a measure of the cell number, since the DNA content/nucleus is constant (34) ; an indication of the average cell composition has then been obtained by relating the other cellular components to DNA. This approach has been used to compare the hypertrophy following unilateral nephrectomy with the variations in kidney size and composition produced by variations in the diet. MATERIALS AND METHODS Experimental animals.†" …